The objective of the present proposal is to elucidate the molecular control of the synthesis of the plasma protein, fibrinogen. Experiments are designed to gain insight into the molecular mechanisms of synthesis of fibrinogen and to determine how this multichained protein is assembled within the cell. The cell systems to be investigated are primary hepatocyte cultures taken from fetal rats and selected rat hepatoma cell lines. The areas to be investigated include; (a) the stimulatory role of fragments D and E (plasmin degradative products of fibrin and fibrinogen) in the synthesis of fibrinogen, (b) isolation and characterization of the mRNA coding for each polypeptide of fibrinogen, (c) characterization of the mechanism of polypeptides assembly into intact molecules, and (d) delineation of the processes of secretion and release of fibrinogen from the liver cell.